The growth of EBV-infected B cells in vitro was inhibited by autologous T lymphocytes. Light lymphocytes acted promptly and their effect was independent of proliferation while the heavy, small T cells proliferated and acted only in later stages of the mixed cultures. Their effect was abrogated if irradiated before admixture to the B cells. Involvement of the recognition of EBVdetermined antigens on the B cells will be studied. Cold target inhibition assays with freshly separated human tumor cells as targets showed that in allogeneic combinations the lytic effect of interferon-activated lymphocytes in short-term tests are initiated through recognition of alloantigens. Blood lymphocytes from patients were separated on the basis of density and tested for lysis of allogeneic and autologous noncultivated tumor cells. Regularly the allo-effect was strongest in the light fraction. In contrast the autoreactivity was stronger with the small, dense lymphocytes in a number of experiments. The characteristics of the autotumor killing lymphocytes will be studied. The generation of anti-K562 and anti-Daudi cytotoxicity differed in mixed lymphocyte cultures. The latter paralleled the generation of the alloreactive potential in that E-rosetting T cells were the precursors. On the contrary, the anti-K562 effect was stronger in the E-negative subset. The lytic potential was generated mainly in the population with low cell density, while the dense lymphocytes showed mostly proliferative responses. Clones will be grown from these subsets and analyzed for target selectivity. Tumor promotors were shown to enhance the natural cytotoxicity of human lymphocytes. The effect was not mediated through induction of interferon production in the population. The details of the activation mechanism will be studied. The recognition of methylcholanthrene sarcoma cells by cytotoxic lymphocytes was studied with regard to the H-2 restriction phenomenon. An F1 tumor and its sublines selected for loss of oneof the parental alloantigen complexes were used. H-2 restriction of cytolytic T cells could be shown in vitro and also in graft neutralization assays in vivo. As a next step passive transfer of immunity with lymphocyte subsets will be performed.